Endothelial cells, which line all blood contacting surfaces in the body, control many aspects of the vasculature ranging from vascular tone to coagulation to inflammation. Endothelial cells also play a guiding role in angiogenesis, the growth of new blood vessels from existing vessels. Endothelial cells produce and secrete angiogenic growth factors such as fibroblast growth factor-2 (FGF2), which in conjunction with many other signals induce endothelial cells to invade the surrounding tissue, proliferate, and develop into new blood vessels. Angiogenesis can be both helpful and harmful. In wound healing, angiogenesis is required in the wound site for rapid healing, whereas in cancer, angiogenesis blockade can starve a tumor and prevent its growth.
Recently, various treatment techniques have been explored to accelerate angiogenesis and endothelial cell proliferation. One such technique is the addition of exogenous angiogenic growth factors, such as FGF2 or vascular endothelial cell growth factor (VEGF). However, these techniques have had limited success due to challenges in creating the optimal dose, dose gradient, and timing. Exogenous growth factors are also expensive. Other techniques have been shown to release endogenous angiogenic growth factors from cells. These techniques include low dose laser, inductively coupled pulsed electromagnetic fields, pulsed electromagnetic fields (PEMF), and low dose ionizing radiation (LDIR). Although these techniques are useful for endothelial cell proliferation, they are not desirable because they result in damage to surrounding tissue and cells and/or they need extensive and expensive setup to be generated safely and applied to human tissue. Accordingly, a technique useful for endothelial cell proliferation which does not damage tissue and can be controlled to treat specific areas and specific depths of real tissue would be highly desirable.